title: Generic construction of single component particles that elicit humoural and cellular immune responses without the need for adjuvants.
abstract: Insoluble, pure protein particles could be advantageous as single-entity vaccines or as carriers for small peptide epitopes. Dense gas anti-solvent precipitation was employed to produce pure protein particles which were found to be insoluble in water. As particulate and multimerized antigens are more immunogenic and hence more advantageous for vaccination, particles were produced via this method using ovalbumin as a model antigen. The particles produced had a mean diameter of approximately 300nm, and remained as discrete particles at low pH. At neutral pH or in the presence of electrolyte, the particles exhibited predictable flocculation behaviour to produce aggregates 1-5microm in diameter. Immunisation of mice with these flocculates elicited specific ovalbumin antibody production, T-cell proliferation and a cytotoxic T-cell response, all in the absence of adjuvant. Thus, dense gas processing could be used as a generic method to produce pure protein particulate vaccines.
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: White
authors.forename: F
authors.initials: F
authors.lastname: Anastasopoulos
authors.forename: J E
authors.initials: JE
authors.lastname: Church
authors.forename: C-Y
authors.initials: CY
authors.lastname: Kuo
authors.forename: B J
authors.initials: BJ
authors.lastname: Boyd
authors.forename: P L C
authors.initials: PL
authors.lastname: Hickey
authors.forename: L Sze
authors.initials: LS
authors.lastname: Tu
authors.forename: P
authors.initials: P
authors.lastname: Burns
authors.forename: A M
authors.initials: AM
authors.lastname: Lew
authors.forename: W R
authors.initials: WR
authors.lastname: Heath
authors.forename: G M
authors.initials: GM
authors.lastname: Davey
authors.forename: C W
authors.initials: CW
authors.lastname: Pouton
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical; D002645:Chickens; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization; D007271:Injections, Intradermal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D052638:Particulate Matter / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D052638:Particulate Matter; D014612:Vaccines; D010047:Ovalbumin; D009113:Muramidase